This multi-disciplinary, multi-national HIVRAD proposal will exploit the favorable attributes of currently available vaccines to explore immunization strategies against HIV. The measles virus (MV), yellow virus (YFV), modified vaccinia virus Ankara (MVA) and varicella zooster virus (VZV) vaccines will be adapted as vectors for the expression of SIV and HIV, antigens, and characterized for their ability to elicit durable and protective immune responses in experimental animals. Project 1 (Enhancing the Magnitude and Longevity of Vaccine-Induced Immune Responses) at Emory University will utilizes recent insights into antigen processing and presentation and the processes of initiation and maintenance of immune responses to design more effective HIV immunogens. Recombinant MVA-HIV vectors will be used to probe the determinants of immunologic memory. Project 2 (Recombinant YFV as a Candidate AIDS Vaccine), at the University of California, will adapt and optimize the YFV vaccine for the expression of HIV and SIV antigens. Project 3 (Recombinant Measles Virus as a Candidate AIDS Vaccine), at the University of Zurich and the Institute Pasteur will adapt attenuated MV vaccines as vectors to express HIV and SIV antigens. An Affiliated Project will explore the ability of recombinant VZVs that express HIV antigens to elicit favorable, long-lasting immune responses in non-human primates. An immunology Core at Emory University will analyze the immunogenicity of recombinant HIV/SIV vaccines in non-human primates, using quantitative, state-of-the-art assays of cellular immune responses. An Animal Trials Core at the Yerkes Region Primate Research Center and Emory Vaccine Center will oversee the care of non-human primates participating in vaccine studies and conduct virologic analyses of vaccine vector replication, and SHIV virus infection and levels of replication in experimentally challenged animals. An Administrative and Data Management Core will coordinate the HIVRAD projects and facilitate communication of ideas and experimental results between investigators.